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Effects of Rhazya Stricta plant organic extracts on human induced pluripotent stem cells derived neural stem cells.

ABSTRACT: Rhazya Stricta (R. stricta) has been employed as a natural remedy for several diseases for centuries. Numerous studies revealed that R. stricta extracts contain alkaloids, tannins, and flavonoids that possess antimicrobial, anticancer, antihypertensive, and antioxidant activities. In this study, we examined the effects of organic extracts from different parts of R. stricta plant on human pluripotent stem cells (hiPSCs)-derived neural stem cells (NSCs) for medical purposes. NSCs were incubated with different concentrations of organic extracts from the leaves, stem, and fruits, and we assessed the growth and viability of the cells by using MTS assay and the chemical composition of the potential plant extract by using gas chromatography-mass spectrometry (GC/MS). Our results revealed that the methanolic extract from the stem increased NSCs growth significantly, particularly at a concentration of 25 μg/ml. GC/MS analysis was utilized to identify the potential compounds of the methanolic extract. In conclusion, our results demonstrated for the first time that methanolic stem extract of R. stricta contains compounds that can positively impact NSCs growth. These compounds can be further investigated to determine the potential bioactive compounds that can be used for research and medical purposes.

SUBMITTER: Alawad AO

PROVIDER: S-EPMC10361509 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Effects of Rhazya Stricta plant organic extracts on human induced pluripotent stem cells derived neural stem cells.

Alawad Abdullah Othman AO Alagrafi Faisal Sultan FS Alfahad Ahmed Jaman AJ Alamari Hala Abdulrahman HA Alghamdi Fatimah Othman FO Fallatah Hussam Mokhtar HM Aodah Alhassan Hamood AH Alyousef Sultan Suleiman SS Bakhrebah Muhammed Adnan MA Alanazi Ibrahim Oqla IO Fallatah Mohannad Mokhtar MM

PloS one 20230721 7

Rhazya Stricta (R. stricta) has been employed as a natural remedy for several diseases for centuries. Numerous studies revealed that R. stricta extracts contain alkaloids, tannins, and flavonoids that possess antimicrobial, anticancer, antihypertensive, and antioxidant activities. In this study, we examined the effects of organic extracts from different parts of R. stricta plant on human pluripotent stem cells (hiPSCs)-derived neural stem cells (NSCs) for medical purposes. NSCs were incubated wi ...[more]

PMID: 37478090

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Project description:The latest coronavirus pandemic (SARS-CoV-2) poses an exceptional threat to human health and society worldwide. The coronavirus (SARS-CoV-2) spike (S) protein, which is required for viral-host cell penetration, might be considered a promising and suitable target for treatment. In this study, we utilized the nonalkaloid fraction of the medicinal plant Rhazya stricta to computationally investigate its antiviral activity against SARS-CoV-2. Molecular docking and molecular dynamics simulations were the main tools used to examine the binding interactions of the compounds isolated by HPLC analysis. Ceftazidime was utilized as a reference control, which showed high potency against the SARS-CoV-2 receptor binding domain (RBD) in an in vitro study. The five compounds (CID:1, CID:2, CID:3, CID:4, and CID:5) exhibited remarkable binding affinities (CID:1, - 8.9; CID:2, - 8.7; and CID:3, 4, and 5, - 8.5 kcal/mol) compared to the control compound (- 6.2 kcal/mol). MD simulations over a period of 200 ns further corroborated that certain interactions occurred with the five compounds and the nonalkaloidal compounds retained their positions within the RBD active site. CID:2, CID:4, and CID:5 demonstrated high stability and less variance, while CID:1 and CID:3 were less stable than ceftazidime. The average number of hydrogen bonds formed per timeframe by CID:1, CID:2, CID:3, and CID:5 (0.914, 0.451, 1.566, and 1.755, respectively) were greater than that formed by ceftazidime (0.317). The total binding free energy calculations revealed that the five compounds interacted more strongly within RBD residues (CID:1 = - 68.8, CID:2 = - 71.6, CID:3 = - 74.9, CID:4 = - 75.4, CID:5 = - 60.9 kJ/mol) than ceftazidime (- 34.5 kJ/mol). The drug-like properties of the selected compounds were relatively similar to those of ceftazidime, and the toxicity predictions categorized these compounds into less toxic classes. Structural similarity and functional group analyses suggested that the presence of more H-acceptor atoms, electronegative atoms, acidic oxygen groups, and nitrogen atoms in amide or aromatic groups were common among the compounds with the lowest binding affinities. In conclusion, this in silico work predicts for the first time the potential of using five R. stricta nonalkaloid compounds as a treatment strategy to control SARS-CoV-2 viral entry.

Project description:BackgroundClimate change is predicted to be a serious threat to agriculture due to the need for crops to be able to tolerate increased heat stress. Desert plants have already adapted to high levels of heat stress so they make excellent systems for identifying genes involved in thermotolerance. Rhazya stricta is an evergreen shrub that is native to extremely hot regions across Western and South Asia, making it an excellent system for examining plant responses to heat stress. Transcriptomes of apical and mature leaves of R. stricta were analyzed at different temperatures during several time points of the day to detect heat response mechanisms that might confer thermotolerance and protection of the plant photosynthetic apparatus.ResultsBiological pathways that were crosstalking during the day involved the biosynthesis of several heat stress-related compounds, including soluble sugars, polyols, secondary metabolites, phenolics and methionine. Highly downregulated leaf transcripts at the hottest time of the day (40-42.4 °C) included genes encoding cyclin, cytochrome p450/secologanin synthase and U-box containing proteins, while upregulated, abundant transcripts included genes encoding heat shock proteins (HSPs), chaperones, UDP-glycosyltransferase, aquaporins and protein transparent testa 12. The upregulation of transcripts encoding HSPs, chaperones and UDP-glucosyltransferase and downregulation of transcripts encoding U-box containing proteins likely contributed to thermotolerance in R. stricta leaf by correcting protein folding and preventing protein degradation. Transcription factors that may regulate expression of genes encoding HSPs and chaperones under heat stress included HSFA2 to 4, AP2-EREBP and WRKY27.ConclusionThis study contributed new insights into the regulatory mechanisms of thermotolerance in the wild plant species R. stricta, an arid land, perennial evergreen shrub common in the Arabian Peninsula and Indian subcontinent. Enzymes from several pathways are interacting in the biosynthesis of soluble sugars, polyols, secondary metabolites, phenolics and methionine and are the primary contributors to thermotolerance in this species.

Project description:Hepatitis B virus (HBV) causes acute and chronic liver diseases, leading to cirrhosis and hepatocellular carcinoma. Although direct-acting nucleoside analogs, such as lamivudine (LAM), adefovir and famciclovir, are available, emergence of drug-resistance due to mutations in HBV polymerase (POL) restricts their further use. Alternatively, numerous plant products and compounds isolated from plants have been reported to confer anti-HBV efficacies without any sign of resistance in vitro or in vivo. As, flavonoids and alkaloids are the most widely reported antivirals, the anti-HBV activities of the flavonoid acacetin (ACT) and the alkaloid acetyl-β-carboline (ABC) from the aerial parts of Rhazya stricta were assessed in the present study. Both compounds were isolated from the ethyl acetate fraction of the total methanol extract using column and thin-layer chromatography, and their structures were determined by nuclear magnetic resonance spectroscopy (NMR). Both compounds (at 6.25-50 µg/ml) showed a lack of hepatocytotoxicity in cultured HepG2.2.15 cells. Anti-HBV ELISA [hepatitis B surface antigen (HBsAg) and hepatitis B pre-core-antigen (HBeAg)] on HepG.2.2.15 cells following treatment with selected concentrations (12.5, 25 and 50 µg/ml) of both compounds showed dose- and time-dependent anti-HBV activities. Compared with those in the untreated control at day 5, ACT and ABC (25 µg/ml, each) maximally inhibited HBsAg synthesis by 43.4 and 48.7%, respectively, whilst also maximally inhibiting HBeAg synthesis by 41.2 and 44.2%, respectively, in HepG2.2.15 cells. Comparatively, quercetin and LAM (standards; POL inhibitors) suppressed HBsAg (63.9 and 60.2%, respectively) and HBeAg synthesis (87.1 and 84.3%, respectively) by larger magnitudes. Molecular docking of ACT and ABC structures performed in AutoDock revealed their hydrogen bonding with the drug-sensitive [wild-type (wt)-POL] 'Tyr-Met-Asp-Asp' motif, in addition to the drug-resistant [mutant (mut)-POL] 'Tyr-Ile-Asp-Asp' motif residues of the polymerase binding-pocket, along with other electrostatic interactions. In the wt-POL complex, both compounds showed good interactions with Asp205. In the mut-POL complex, ACT and ABC interacted with Tyr203-Asp205 and Tyr203-Ile204, respectively. In conclusion, to the best of our knowledge, the present study demonstrates anti-HBV efficacies of ACT and ABC in vitro for the first time, endorsed by in silico data. However, further molecular and pharmacological studies are required to validate their pre-clinical therapeutic potential.

Dataset Information

Effects of Rhazya Stricta plant organic extracts on human induced pluripotent stem cells derived neural stem cells.

Publications

Effects of Rhazya Stricta plant organic extracts on human induced pluripotent stem cells derived neural stem cells.

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